Download - Amoebiasis by JITENDRA BHANGALE
9/2/2012
1
© 2010 Delmar, Cengage Learning1
By- Jitendra Bhangale
Assistant Professor & Head,
Department of Pharmacology,
Smt N. M. Padalia Pharmacy College,
Ahmedabad
© 2010 Delmar, Cengage Learning2
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
9/2/2012
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© 2010 Delmar, Cengage Learning3
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Amebiasis is a protozoal infection of the intestinal tract
that occurs due to ingestion of foods or water
contaminated with Entameba Histolytica cysts
© 2010 Delmar, Cengage Learning4
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Entamoeba histolytica exists in two forms:
1. Cysts (infective):
can survive outside the human body.
transform to trophozoites.
2. Trophozoites (non-infective; invasive):
Can reproduce
They may feed on intestinal bacteria or invade and
ulcerate wall of large intestine, and may migrate
to liver or other tissues.
transform to cysts which are excreted in feces.
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© 2010 Delmar, Cengage Learning5
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
1. Cysts ingestion.
2. Formation of trophozoites
3. Penetration of intestinal wall
4. Multiplication of trophozoites within colon wall.
5. Systemic invasion.
6. Cyst formation in rectum and excretion in feces.
© 2010 Delmar, Cengage Learning6
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
9/2/2012
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© 2010 Delmar, Cengage Learning7
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Asymptomatic Intestinal infection
(Carriers, passing cysts)
Mild to moderate intestinal disease
(Nondysenteric Colitis)
Severe Intestinal infection
(Dysentery)
Hepatic abscess, ameboma (localized granulomatous
lesion of colon) and other extraintestinal disease
© 2010 Delmar, Cengage Learning8
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
9/2/2012
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© 2010 Delmar, Cengage Learning9
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Luminal Amebicides
Tissue or systemic amebicides
Mixed Amebicides
© 2010 Delmar, Cengage Learning10
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Acts on the parasites in the lumen of the bowl.
used for treatment of asymptomatic amebiasis.
Include
Diloxanide Furoate
Iodoquinol
Antibiotics
Paromomycin
Tetracyclines
Erythromycin
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© 2010 Delmar, Cengage Learning11
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
acts on the intestinal wall and liver (or any other extra-
intestinal tissue).
Used for treatment of systemic form of the disease
(intestinal wall infection or liver abscesses).
Emetine
Dehydroemetine
Chloroquine (liver only)
© 2010 Delmar, Cengage Learning12
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Effective against both luminal and systemic forms of the
disease.
Although luminal concentration is too low for single drug
treatment.
Metronidazol
Tinidazole
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© 2010 Delmar, Cengage Learning13
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Mixed amoebicide.
Drug of choice for intestinal & extraintestinal
amoebiasis.
Acts on trophozoites.
Has no effect on cysts.
Nitro group of metronidazole is reduced by protozoan
leading to cytotoxic reduced product that binds to
DNA and proteins resulting into parasite death.
© 2010 Delmar, Cengage Learning14
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Pharmacokinetics
Given orally or IV.
Absorption is rapid and complete.
Due to rapid absorption from GIT, not reliably effective
against luminal parasites.
Wide distribution to all tissues and body fluids (CSF,
saliva, milk).
Plasma protein binding is low ( < 20%).
Plasma half life is 8 h
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© 2010 Delmar, Cengage Learning15
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Pharmacokinetics
Metabolized in liver by mixed function oxidase followed
by glucouroidation.
Excreted in urine as unchanged drug plus metabolites.
Clearance is decreased in liver impairment.
Tinidazole has longer duration, simpler dosing
regimen, less toxicity, than metronidazole, but is equally
active.
© 2010 Delmar, Cengage Learning16
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Clinical uses:-
Extraluminal amoebiasis (combined with luminal
amebicide).
Giardiasis
Trichomoniasis
Broad spectrum of Anaerobic bacteria e.g.,
Helicobacter pylori infection
Pseudomembranous colitis (Clostridium defficile).
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© 2010 Delmar, Cengage Learning17
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Adverse effect:-
1. GIT:
Nausea
Vomiting
Dry mouth
Metallic taste
Diarrhoea
Oral Thrush (Moniliasis, yeast infection).
© 2010 Delmar, Cengage Learning18
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
2. CNS: Neurotoxicological effect
Insomnia, dizziness
peripheral neuropathy, paresthesia
encphalopathy, convulsion ( IV infusion, rare).
3. Dysuria, dark urine.
4. Neutropenia
5. Disulfiram-like effect if taken with alcohol.
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© 2010 Delmar, Cengage Learning19
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Disulfiram like -effect
When metronidazole is given with alcohol abdominal
distress, nausea, vomiting, flushing, or headache,
tachycardia, hyperventilation
© 2010 Delmar, Cengage Learning20
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Drug interactions:
Enzyme inhibitors (cimetidine, ketoconazole)
increase duration of action of metronidazole
Inducers (phenytoin and phenobarbitone).
inhibits CYP family 2C9 & 3A4
potentiate anticoagulant effect of warfarin.
potentiates lithium toxicity.
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© 2010 Delmar, Cengage Learning21
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
CONTRAINDICATIONS / PRECAUTIONS:
Pregnancy and nursing women.
Alcohol intake
CNS diseases
Severe hepatic disease
Severe renal disease
© 2010 Delmar, Cengage Learning22
Chemistry:
Emetine hydrochloride is a plant alkaloid derived from
ipeca.
Dehydroemetine is a synthetic analogue
Pharmacokinetics:
Erratic oral absorption.
Given preferably subcutaneously but could be given
by IM, NEVER I.V.
Plasma half life is 5 days.
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
9/2/2012
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© 2010 Delmar, Cengage Learning23
Concentrated in Liver, Lungs, Spleen, Kidney, Cardiac
muscle and Intestinal wall.
Metabolized & Excreted slowly via kidney so it has a
cumulative effect.
Trace amounts could be detected in urine 1-2 month
after last dose.
Should not be used for more than 10 days (usually 3-
5 days).
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
© 2010 Delmar, Cengage Learning24
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Mechanism
Act on tissue trophozoites causing irreversible block of
protein synthesis.
Adverse effect:-
Dehydroemetine is less toxic than emetine
GIT: nausea, vomiting, diarrhoea.
Neuromuscular weakness
Serious toxicities: cardiotoxicity
cardiac arrhythmias,
Hypotension, heart failure
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© 2010 Delmar, Cengage Learning25
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Clinical uses:-
Amoebic liver abscess.
Intestinal wall infections.
Severe forms of amebiasis acute amoebic dysentery
dehydroemetine is preferable due to less toxicity (3-5
days).
© 2010 Delmar, Cengage Learning26
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Contraindication:-
Heart disease
Kidney disease
Pregnancy
Children
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© 2010 Delmar, Cengage Learning27
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Antiamebic drug
Antimalarial drug
Used in combination with metronidazole and luminal
amebicide for amebic liver diseases.
© 2010 Delmar, Cengage Learning28
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
acts on the luminal parasites
used for treatment of asymptomatic amebiasis.
Include
Diloxanide Furoate
Iodoquinol
Antibiotics
Paromomycin
Tetracyclines
Erythromycin
9/2/2012
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© 2010 Delmar, Cengage Learning29
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Chemistry
Ester of diloxanide + furoic acid .
Pharmacokinetics
Given orally.
Split in the intestine, most of diloxanide is absorbed,
conjugated to form a glucoronide which is excreted in
urine (90%).
The unabsorbed diloxanide is the amoebicidal agent
(10%).
© 2010 Delmar, Cengage Learning30
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Pharmacodynamics
Unkown mechanism of action
Direct amoebicidal action against luminal forms.
Not active against trophozoites intestinal wall or
extraintestinal tissues.
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© 2010 Delmar, Cengage Learning31
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Therapeutic uses:-
Drug of choice for asymptomatic intestinal infection.
For eradication of infection given along with all forms
of amebiasis.
Dose: 500 mg three times/day for 10 days.
© 2010 Delmar, Cengage Learning32
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Adverse effect:-
Flatulence
Nausea, vomiting, abdominal cramps.
No serious adverse effects
Contraindications:
Pregnancy
Children (less than 2 years).
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© 2010 Delmar, Cengage Learning33
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Aminoglycoside, not absorbed.
Effective against luminal forms of ameba
Mechanism of action
Direct amebicidal action (causes leakage by its action
on cell membrane of parasite).
Indirect killing of bacterial flora essential for
proliferation of pathogenic amoebae.
© 2010 Delmar, Cengage Learning34
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Kinetics
Orally
Not significantly absorbed from the GIT
Small amount absorbed is excreted unchanged in
urine (may accumulate with renal insufficiency).
Adverse effects
Gastrointestinal distress and diarrhea.
Precautions
Severe renal disease
Patients with GIT ulceration
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© 2010 Delmar, Cengage Learning35
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Very weak direct amoebicidal action.
Mainly act indirectly on bacterial flora.
Used in severe cases of amoebic dysentery not
responding to metronidazole combined with
dehydroemetine.
© 2010 Delmar, Cengage Learning36
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Mechanism of action
Effective against organisms in GIT only Not intestinal
wall or liver.
Pharmacokinetics
Absorption is poor (90%), excreted in feces.
10% enter circulation, excreted as glucouronide in
urine. Half life is 11-14 h
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© 2010 Delmar, Cengage Learning37
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Uses
lumen amoebicide.
For eradication of infection given along with tissue
amoebicide (metronidazole).
© 2010 Delmar, Cengage Learning38
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Adverse effect:-
Peripheral neuropathy including optic neuritis
GIT: Nausea, vomiting, diarrhoea.
Enlargement of the thyroid gland.
Agranulocytosis.
Iodine sensitivity.
interference with thyroid function tests (increase
protein-bound serum iodine, decrease in measured 131I
uptake).
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© 2010 Delmar, Cengage Learning39
By J. O. Bhangale, Head, Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, A’bad
Contraindication:-
Optic neuropathy
Thyroid disease
Severe liver disease
Severe kidney disease
discontinued if it produces persistent diarrhea or signs
of iodine toxicity (dermatitis, urticaria, pruritus, fever)
© 2010 Delmar, Cengage Learning40
By Jitendra BhangaleAsst. Prof. Dept of Pharmacology, Smt N. M. Padalia Pharmacy College, Ahmedabad